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K. Hotta



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    MINI 10 - ALK and EGFR (ID 105)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      MINI10.10 - A Multicenter Prospective Biomarker Study in Afatinib-Treated Patients with EGFR-Mutation Positive Non-Small Cell Lung Cancer (ID 472)

      16:45 - 18:15  |  Author(s): K. Hotta

      • Abstract
      • Presentation
      • Slides

      Background:
      Afatinib is an oral, irreversible ErbB family blocker and one of the key drugs for patients with EGFR mutation positive advanced non-small cell lung cancer (NSCLC). Although treatment with afatinib has a clinical benefit for these patients, such individuals inevitably develop drug resistance as with other TKIs. This is a multicenter prospective biomarker study to inform the usefulness of noninvasive liquid biopsy in the treatment of EGFR-tyrosine kinase inhibitors (EGFR-TKIs) and explore the molecular mechanism of acquired-resistance against afatinib.

      Methods:
      Eligible patients were EGFR-TKIs naïve and had histologically and cytologically confirmed stage IIIB/IV adenocarcinoma of the lung with activating EGFR mutations. Patients remained on afatinib treatment until disease progression or unacceptable toxicity. Tumor samples were collected upon before afatinib treatment and after disease progression. Plasma samples were collected upon before and during afatinib treatment (4 and 24 weeks after initiation) and after disease progression. DNA derived both from tumors and plasma was analyzed using Scorpion-ARMS (ARMS), digital PCR (dPCR) and next generation sequencing (NGS). We used a nanofluidic dPCR system (BioMark HD System; Fluidigm) with a digital chip to detect activating or resistance mutations of EGFR in a quantitative and highly sensitive manner. NGS on an Ion Torrent PGM device (Thermo Fisher Scientific) was applied to detect target molecules which contribute to the survival and growth of lung cancer cells. We compared the sensitivity of these methods in detection of EGFR activating mutations in plasma DNA.

      Results:
      A total of 35 EGFR mutation positive NSCLC patients were enrolled. Twenty one patients harbored a deletion in exon 19 and fourteen patients had an L858R missense mutation in exon 21. Twenty seven (77.1%) patients had an objective response. In plasma DNA obtained before afatinib treatment, dPCR and NGS detected EGFR activating mutations more sensitively compared with ARMS (83.9% v 58.1%; p <0.005, 74.2% v 58.1%; p =0.059, respectively). Concordance of EGFR activating mutations detected by dPCR and NGS was 26/31 (84%) (kappa value: 0.52). All of the mutation type detected by NGS on plasma DNA completely corresponded to that found in matching tumor tissue by NGS. As of March 2015, serial plasma DNA was analyzed in 9 patients. The copy number of activating mutation was markedly decreased in 5 of 9 patients.

      Conclusion:
      EGFR activating mutations in plasma DNA were frequently detected by dPCR or NGS. We will present the detailed data for monitoring mutation load in plasma DNA during the afatinib treatment.

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    P1.02 - Poster Session/ Treatment of Localized Disease – NSCLC (ID 209)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Localized Disease - NSCLC
    • Presentations: 1
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      P1.02-032 - Randomized Feasibility Study of S-1 for Adjuvant Chemotherapy in Completely-Resected Stage IA Non-Small-Cell Lung Cancer (SLCG 0701) (ID 754)

      09:30 - 17:00  |  Author(s): K. Hotta

      • Abstract

      Background:
      The aim of this multicenter study (the Setouchi Lung Cancer Group Study 0701) was to determine the feasible administration schedule of S-1, an oral fluoropyrimidine, for adjuvant chemotherapy in patients with completely-resected pathological stage IA (tumor diameter, 2 to 3 cm) non-small-cell lung cancer (NSCLC).

      Methods:
      Patients were randomly assigned to receive an adjuvant chemotherapy of either 4-week oral administration of S-1 (80 mg/m2/day) followed by 2-week rest (group A), or 2-week oral administration of S-1 (80 mg/m2/day) followed by one week rest (Group B). The duration of adjuvant chemotherapy was one year in both arms. The primary endpoint was feasibility.

      Results:
      Figure 1 Eighty patients were enrolled, of whom 76 were received S-1 treatment. The treatment completion rates were 49.4% [95% confidential interval (CI), 32.8 to 65.9%] in group A and 52.1 % (95%CI, 35.5 to 68.6%) in group B (P = 0.4). The relative dose intensities were 40.4% (95%CI, 20.3 to 60.5%) in group A and 53.5% (95%CI, 37.7 to 69.3%) in group B (P = 0.4). There were no treatment-related deaths. Patients with grade 3/4 toxicities were significantly more frequent in group A (40.5%) than group B (15.4%, P = 0.02). The 2-year relapse-free survival rates were 97.5% in group A and 92.5% in group B, and the 2-year overall survival rates were 100% in both groups.



      Conclusion:
      Two-week oral administration of S-1 followed by one week rest for one year may be more feasible for adjuvant chemotherapy in patients with completely-resected stage IA (T diameter, 2 to 3 cm) NSCLC.